rs734187

Variant names:

• chr10-33195768-G-A
• rs734187
• NM_003873.7:c.1924+1882C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003873.7(NRP1):​c.1924+1882C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,984 control chromosomes in the GnomAD database, including 5,645 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5645 hom., cov: 32)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 9 publications found

Genes affected

NRP1 (HGNC:8004): (neuropilin 1) This gene encodes one of two neuropilins, which contain specific protein domains which allow them to participate in several different types of signaling pathways that control cell migration. Neuropilins contain a large N-terminal extracellular domain, made up of complement-binding, coagulation factor V/VIII, and meprin domains. These proteins also contains a short membrane-spanning domain and a small cytoplasmic domain. Neuropilins bind many ligands and various types of co-receptors; they affect cell survival, migration, and attraction. Some of the ligands and co-receptors bound by neuropilins are vascular endothelial growth factor (VEGF) and semaphorin family members. This protein has also been determined to act as a co-receptor for SARS-CoV-2 (which causes COVID-19) to infect host cells. [provided by RefSeq, Nov 2020]

NRP1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003873.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP1	NM_003873.7	MANE Select	c.1924+1882C>T		intron	N/A	NP_003864.5
	NRP1	NM_001244972.2		c.1903+1882C>T		intron	N/A	NP_001231901.2
	NRP1	NM_001244973.2		c.1903+1882C>T		intron	N/A	NP_001231902.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP1	ENST00000374867.7	TSL:1 MANE Select	c.1924+1882C>T		intron	N/A	ENSP00000364001.2
	NRP1	ENST00000395995.5	TSL:1	c.1924+1882C>T		intron	N/A	ENSP00000379317.1
	NRP1	ENST00000374875.5	TSL:1	c.1360+1882C>T		intron	N/A	ENSP00000364009.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39753 AN: 151866 Hom.: 5644 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.298

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.262 AC: 39768 AN: 151984 Hom.: 5645 Cov.: 32 AF XY: 0.260 AC XY: 19335 AN XY: 74286

African (AFR) AF: 0.257 AC: 10659 AN: 41428

American (AMR) AF: 0.201 AC: 3065 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3468

East Asian (EAS) AF: 0.643 AC: 3305 AN: 5142

South Asian (SAS) AF: 0.359 AC: 1729 AN: 4816

European-Finnish (FIN) AF: 0.203 AC: 2146 AN: 10572

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16954 AN: 67974

Other (OTH) AF: 0.300 AC: 634 AN: 2114

Alfa AF: 0.260 Hom.: 21049

Bravo AF: 0.263

Asia WGS AF: 0.478 AC: 1657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.49
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs734187; hg19: chr10-33484696;